# Punctuated evolution of prostate cancer genomes

Source: https://onco.cc/key-papers/paper-baca-punctuated-evolution-chromoplexy-cell-2013/  
OnCo record `paper-baca-punctuated-evolution-chromoplexy-cell-2013` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cancer is usually described as accumulating damage one change at a time. Sequencing 57 whole prostate cancer genomes showed something else: chains of translocations and deletions that happen together in one burst, disrupting several cancer genes at once.

## Summary

Sylvan Baca, Levi Garraway, Mark Rubin and colleagues sequenced the genomes of 57 prostate tumours and matched normal tissue, then modelled how the rearrangements they found could have arisen. Translocations and deletions were abundant and highly interdependent, arriving in coordinated chains the authors named chromoplexy.

The consequence is a model of punctuated rather than gradual evolution: a small number of events can derange a large amount of genome at once, and the classical picture of stepwise mutation accumulation does not describe how this cancer is built. By ordering the clonal hierarchy of lesions the authors also charted a path of oncogenic events, which is the beginning of the timing work that Gundem extended to metastasis.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Also known as: Baca 2013; chromoplexy; chromoplexy prostate cancer
- Tags: prostate-evidence
- Journal: Cell
- Year: 2013
- DOI: 10.1016/j.cell.2013.03.021
- Authors: Baca SC, Prandi D, Lawrence MS, et al.
- Findings: Whole-genome sequencing of 57 prostate tumours and matched normal tissue characterised somatic alterations and how they accumulate during oncogenesis and progression.; Modelling the genesis of genomic rearrangements identified abundant DNA translocations and deletions arising in a highly interdependent manner, a phenomenon the authors named chromoplexy.; Chromoplexy frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately.; The modelling suggests chromoplexy may induce considerable genomic derangement over relatively few events, supporting a model of punctuated cancer evolution.; Characterising the clonal hierarchy of genomic lesions charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis.
- What it means: A different picture of how a cancer genome is built, and one that explains why prostate cancer has few point mutations and a great deal of structural damage. It is also why whole-genome rather than exome sequencing is the right assay for this disease.
- Caveats: 57 genomes, mostly primary tumours; the frequency of chromoplexy across the disease is not established here.; Chromoplexy is inferred from the pattern of rearrangements by modelling rather than observed as it happens.; No treatment follows from the finding; it changes the model of the disease rather than what is done about it.

## Sources

- Cell 2013: https://doi.org/10.1016/j.cell.2013.03.021
- PubMed: https://pubmed.ncbi.nlm.nih.gov/23622249/

## Connected records

- key papers: [The evolutionary history of lethal metastatic prostate cancer](https://onco.cc/key-papers/paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015/), [The mutational landscape of lethal castration-resistant prostate cancer](https://onco.cc/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/)
- roadmaps: [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/)
- cancers: [Localised prostate cancer, high and very high risk](https://onco.cc/cancers/prostate-high-risk/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- targets: [ERG](https://onco.cc/targets/erg/), [TMPRSS2](https://onco.cc/targets/tmprss2/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/), [Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine](https://onco.cc/institutions/weill-cornell-meyer-cancer-center/)
- terms: [Chromoplexy](https://onco.cc/terms/chromoplexy/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- journals: [Cell](https://onco.cc/journals/cell/)

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